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FLUDARA 50MG POWDER FOR SOLUTION FOR INJECTION OR INFUSION

Active substance(s): FLUDARABINE PHOSPHATE

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Package leaflet: information for the user

50 mg

powder for solution for injection or infusion
Fludarabine phosphate

Read all of this leaflet carefully
before you start taking this medicine
because it contains important
information for you.
 Keep this leaflet. You may need to read
it again.
 If you have any further questions,
ask your doctor or pharmacist.
 If you get any side effects, talk to your
doctor or pharmacist. This includes
any possible side effects not listed in
this leaflet. See section 4.
What is in this leaflet
1. What Fludara is and what it is used for
2. What you need to know before you are
given Fludara
3. How to use Fludara
4. Possible side effects
5. How to store Fludara
6. Contents of the pack and other
information

1. What Fludara is and what it is
used for
Fludara contains the active substance
fludarabine phosphate which stops the
growth of new cancer cells. All cells of the
body produce new cells like themselves
by dividing. Fludara is taken up by the
cancer cells and stops them dividing.
In cancers of the white blood cells
(such as chronic lymphocytic leukaemia),
the body produces many abnormal white
blood cells (lymphocytes) and lymph
nodes start to grow in various parts of
the body. The abnormal white blood cells
cannot carry out the normal disease
fighting functions and may push aside
healthy blood cells. This can result in
infections, a decrease in number of red
blood cells (anaemia), bruising, severe
bleeding or even organ failure.
Fludara is used in the treatment of B-cell
chronic lymphocytic leukaemia (B-CLL)
in patients with sufficient healthy blood
cell production.
First treatment for chronic lymphocytic
leukaemia with Fludara should only be
started in patients with advanced disease
having disease-related symptoms or
evidence of disease progression.

2. What you need to know
before you are given Fludara
Do not use Fludara:
 if you are allergic to fludarabine
phosphate or any of the other
ingredients of this medicine (listed in
section 6).
 if you are breast-feeding.
 if you have severe kidney problems.
 if your red blood cell count is low,
because of a type of anaemia
(decompensated haemolytic
anaemia). Your doctor will have told
you if you have this condition
Tell your doctor, if you think any of
these may apply to you.
Warnings and precautions
Talk to your doctor before using Fludara.
Take special care with Fludara:
 if your bone marrow is not working
properly or if you have a poorly
functioning or depressed immune
system or a history of serious
infections.
Your doctor may decide to not give you
this medicine, or may take precautions.
 if you feel very unwell, notice any
unusual bruising, more bleeding than
usual after injury, or if you seem to be
catching a lot of infections.
 if during treatment you have a red
to brownish urine, or have a rash
or any blisters on your skin.
 Tell your doctor immediately
These may be signs of a reduction in the
number of blood cells, which may be
caused either by the disease itself or the
therapy.
It can last for up to a year, independent
of whether or not you had treatment with
Fludara before. During treatment with
Fludara also your immune system may
attack different parts of your body, or
your red blood cells (called ‘autoimmune
disorders’). These conditions can be lifethreatening.
If this occurs your doctor will stop
your treatment and you may receive
further medication such as transfusion
of irradiated blood (see below) and
adrenocorticoids.
You will have regular blood tests during
treatment and you will be closely
monitored while you are being treated
with Fludara.

The following information is intended for
healthcare professionals only:
Reconstitution
Fludara should be prepared for parenteral
use by aseptically adding sterile water for
injection. When reconstituted with 2 ml
of sterile water for injection, the powder
should fully dissolve in 15 seconds or
less. Each ml of the resulting solution will
contain 25 mg of fludarabine phosphate,
25 mg of mannitol, and sodium hydroxide
(to adjust the pH to 7.7). The pH range for
the final product is 7.2 - 8.2.

 if you notice any unusual symptoms
of your nervous system such
as disturbed vision, headache,
confusion, seizures.
If Fludara is used for a long time, its effects
on the central nervous system are not
known. However patients treated with the
recommended dose for up to 26 courses
of therapy were able to tolerate it.
When Fludara is used at the
recommended dose, following the
treatment with some other medications
or at the same time as some other
medications, the following adverse
events have been reported: neurological
disorders manifested by headache,
feeling sick (nausea) and vomiting,
seizures, visual disturbances including
vision loss, changes in mental status
(thinking abnormal, confusion, altered
consciousness) and occasionally
neuromuscular disorders manifested
by muscle weakness in your limbs
(including irreversible partial or
complete paralysis) (symptoms of
leukoencephalopathy, acute toxic
leukoencephalopathy or posterior
reversible leukoencephalopathy
syndrome (RPLS)).
In patients on doses four times greater
than recommended blindness, coma
and death have been reported.
Some of these symptoms appeared
delayed around 60 days or more after
treatment had been stopped. In some
patients receiving Fludara doses
higher than the recommended dose,
leukoencephalopathy (LE), acute toxic
leukoencephalopathy (ATL) or posterior
reversible leukoencephalopathy
syndrome (RPLS) have also been
reported. Same symptoms of LE, ATL
or RPLS as above described could occur.
LE, ATL, and RPLS may be irreversible,
life-threatening, or fatal.
Whenever LE, ATL or RPLS is suspected,
your treatment will Fludara will be
stopped for further investigations.
If the diagnosis of LE, ATL, or RPLS is
confirmed, you doctor will permanently
discontinue your treatment with Fludara.
 if you notice any pain in your side,
blood in your urine or reduced
amount of urine.
When your disease is very severe, your
body may not be able to clear all the
waste products from the cells destroyed
by Fludara. This is called tumour lysis
syndrome and can cause kidney failure
and heart problems from the first week
of treatment. Your doctor will be aware of
this and may give you other medicines to
help prevent it.
 if you need to have stem cells
collected and you are being treated
with Fludara (or have been).
 if you need a blood transfusion and
you are being treated with Fludara
(or have been).
In case you need a blood transfusion
your doctor will ensure that you only
receive blood that has been treated
by irradiation. There have been severe
complications and even death, from
transfusions of non-irradiated blood.
 if you notice any changes to your
skin either while you are receiving
this medicine or after you have
finished the therapy.
 if you have or have had skin cancer
it may worsen or flare up again during
Fludara therapy or afterwards. You may
develop skin cancer during or after
Fludara therapy.
Other things to consider, while you
are treated with Fludara:
 Men and women who are fertile
must use effective contraception
during treatment and for at least
6 months afterwards. It cannot be ruled
out that Fludara may harm an unborn
baby. Your doctor will carefully weigh
the benefit of your treatment against
a possible risk for an unborn child and,
if you are pregnant, will only treat you
with Fludara if clearly necessary.
 if you consider or are breastfeeding
you should not start it or continue
while on treatment with Fludara.
 if you need a vaccination, check
with your doctor, because live
vaccinations should be avoided during
and after treatment with Fludara.
 if you have kidney problems or if
you are over 65, you will have regular
blood and/or laboratory tests to check
your kidney function. If your kidney
problems are severe, you will not be
given this medicine at all (see sections
2 and 3).

Dilution
The required dose (calculated on the
basis of the patient‘s body surface) is
drawn up into a syringe.
For intravenous bolus injection this dose
is further diluted in 10 ml sodium chloride
9mg/ml (0.9%). Alternatively, for infusion,
the required dose may be diluted in 100 ml
sodium chloride 9mg/ml (0.9%) and
infused over approximately 30 minutes.
In clinical studies, the product has
been diluted in 100 ml or 125 ml of 5 %
dextrose injection or sodium chloride
9mg/ml (0.9%).

Children and adolescents
The safety and effectiveness of Fludara
in children below the age of 18 years has
not been established. Therefore, Fludara
is not recommended for use in children.
Older patients and Fludara:
People over 65, will have regular tests
for kidney function (see also section 3.
How to use Fludara).
People over 75, will be monitored
especially closely.
Other medicines and Fludara
Tell your doctor if you are taking, have
recently taken or might take any other
medicines, including medicines obtained
without a prescription.
It is especially important to tell your
doctor about:
 pentostatin (deoxycoformycin),
also used to treat B-CLL. Taking these
two drugs together can lead to severe
lung problems.
 dipyridamole, used to prevent
excessive blood clotting or other
similar drugs. They may reduce the
effectiveness of Fludara.
 cytarabine (Ara-C) used to treat
chronic lymphatic leukaemia.
If Fludara is combined with cytarabine,
levels of the active form of Fludara in
leukaemic cells may rise. However,
the overall levels in the blood and its
elimination from the blood were not
shown to have changed.
Pregnancy, breast-feeding and
fertility
Pregnancy
Fludara should not be given to women
who are pregnant because animal
studies and very limited experience in
humans have shown a possible risk of
abnormalities in the unborn baby as well
as early pregnancy loss or premature
delivery.
If you are pregnant or you think you may
be pregnant, tell your doctor immediately.
Your doctor will carefully weigh the benefit
of your treatment against a possible
risk for an unborn child and, if you are
pregnant, will only prescribe Fludara if
clearly necessary.
Breast-feeding
You must not start or continue breast
feeding during your treatment with
Fludara, as this medicine may interfere
with the growth and development of your
baby.
Fertility
Men and women, who are fertile, must
use effective contraception during
treatment and for at least 6 months
afterwards.
Driving and using machines
Some people get tired, feel weak, have
disturbed vision, become confused,
or agitated or have seizures while they are
treated with Fludara. Do not try to drive or
operate machines until you are sure that
you are not affected.
Fludara contains sodium This medicine
contains less than 1mmol sodium per
dose, i.e, essentially sodium free.

3. How to use Fludara
Fludara should be administered under
the supervision of a qualified doctor
experienced in the use of anti-cancer
therapy.
How much Fludara is given
The dose you are given depends on your
body surface area. This is measured in
square metres (m2) and is worked out by
the doctor from your height and weight.
The recommended dose is 25 mg
fludarabine phosphate/m2 body surface
area.
How Fludara is given
Fludara is given in the form of a solution
as an injection or mostly as an infusion.
An infusion means that the medicine is
given directly into the blood stream by
a drip through a vein. One infusion takes
approximately 30 minutes.
Your doctor will make sure that Fludara is
not given beside the vein (paravenously).
However, if this happens, no severe local
adverse events have been reported.
For how long Fludara is given
The dose will be given once a day for
5 consecutive days.
This 5-day course of treatment will be
repeated every 28 days until your doctor
has decided that the best effect has been
achieved (usually after 6 courses).
How long the treatment lasts depends
on how successful your treatment is and
how well you tolerate Fludara. The repeat
course may be delayed if side effects are
a problem.
You will have regular blood tests during
your treatment. Your individual dose will
be carefully adjusted according to the
number of your blood cells and your
response to the therapy. The dosage
may be decreased if side effects are
a problem.

587538
Inspection prior to use
The reconstituted solution is clear and
colourless. It should be visually inspected
before use.
Only clear and colourless solutions
without particles should be used. Fludara
should not be used in case of a defective
container.
Handling and disposal
Fludara should not be handled by
pregnant staff.
Procedures for proper handling should be
followed according to local requirements
for cytotoxic drugs.

Measure bar should be 150mm at 100% scale

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Clearly mark any amendments on one proof and return to MPS

Warning! We cannot accept responsibility for any errors
in this proof after approval. Whilst we take extreme care
at all times to ensure accuracy to our clientʼs brief,
the final responsibility must be taken by our client.
IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING
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Customer

Genzyme UK (Suffolk)

Description

FLUDARA IV 50MG Leaflet

Item Code

587538

Profile

GI200500

Size

200x500mm

Min. Point Size

9pt

Market

UK

Language

English

Proof By

louise.heel

Proof No.

2

Date

10/11/2015

Artwork No.

608991

Colours Used
50 gsm

Folded: 100x26mm

Pharma
Code

N/A

Process Black +25% + 15% tint
Keyline (does not print)

If you have kidney problems or if
you are over the age of 65, you will
have regular tests to check your kidney
function. If your kidneys do not work
properly you may be given this medicine
at a lower dose. If your kidney function
is severely reduced you will not be given
this medicine at all (see section 2).
If any Fludara solution is accidentally
spilt
If any of the Fludara solution comes into
contact with your skin or the lining of your
nose or mouth, wash the area thoroughly
with soap and water. If the solution gets
into your eyes, rinse them thoroughly with
plenty of tap water. Avoid any exposure
by inhalation.
If more Fludara is given than it should
If you may have received an overdose
your doctor will stop the therapy and treat
the symptoms.
High doses can lead to a severely
reduced number of blood cells.
For Fludara given intravenously it has
been reported, that overdose can cause
delayed blindness, coma and even death.
If a dose of Fludara is forgotten
Your doctor will set the times at which you
are to receive this medicine. Talk to your
doctor as soon as possible, if you think
you may have missed a dose.
If you stop using Fludara
You and your doctor may decide to stop
your treatment with Fludara if the side
effects are becoming too severe.
If you have any further questions on the
use of this medicine, ask your doctor or
pharmacist.

4. Possible side effects
Like all medicines, this medicine
can cause side effects, although not
everybody gets them. If you are not sure
what the side effects below are, ask your
doctor to explain them to you.
Some side effects can be life-threatening.
Tell your doctor immediately:
 if you have difficulty breathing, have
a cough, or have chest pain with or
without fever. These may be signs
of an infection of the lungs.
 if you notice any unusual bruising,
more bleeding than usual after injury
or if you seem to be catching a lot
of infections. These may be caused
by a reduced number of blood cells.
This may also lead to an increased
risk of (serious) infections, caused
by organisms, that usually do not
cause disease in healthy persons
(opportunistic infections) including
a late reactivation of viruses, for
example herpes zoster.
 if you notice any pain in your side,
blood in your urine, or reduced amount
of urine. These may be signs of tumour
lysis syndrome (see section 2).
 if you notice any skin and / or
mucous coat reaction with redness,
inflammation, blistering and tissue
break down. These may be signs
of a severe allergic reaction (Lyell’s
syndrome, Stevens-Johnson
syndrome).
 if you have palpitations (if you
suddenly become aware of your heart
beat) or chest pain. These may be
signs of heart problems.
Below are possible side effects by
how common they are. Very common
side effects (may affect more than
1 in 10 people)
 infections (some serious)
 infections due to depressed immune
system (opportunistic infections)
 infection of the lungs (pneumonia)
with possible symptoms like breathing
difficulties and / or cough with or
without fever
 reduction in the number of blood
platelets (thrombocytopenia) with the
possibility of bruising and bleeding
 lowered white blood cell count
(neutropenia)
 lowered red blood cell count
(anaemia)
 cough
 vomiting, diarrhea, feeling sick
(nausea)
 fever
 feeling tired (fatigue)
 weakness
Common side effects (may affect up
to 1 in 10 people)
 other blood related cancers
(myelodysplastic syndrome, acute
myeloid leukaemia). Most patients
with these conditions were previously,
or at the same time or later treated
with other cancer drugs (alkylating
agents, topoisomerase inhibitors)
or radiation therapy.
 bone marrow depression
(myelosuppression)
 severe loss of appetite leading to
weight loss (anorexia)
 numbness or weakness in limbs
(peripheral neuropathy)

 disturbed vision
 inflammation of the inside of the mouth
(stomatitis)
 skin rash
 swelling due to excessive fluid
retention (oedema)
 inflammation of the mucous coat of
the digestive system from the mouth
to the anus (mucositis)
 chills
 generally feeling unwell
Uncommon side effects (may affect up
to 1 in 100 people)
 autoimmune disorder (see section 2)
 tumour lysis syndrome (see section 2)
 confusion
 lung toxicity, scarring throughout
the lungs (pulmonary fibrosis),
inflammation of the lungs
(pneumonitis), shortness of breath
(dyspnoea)
 bleeding in the stomach or intestines
 abnormal levels of the liver or
pancreas enzymes
Rare side effects (may affect up to
1 in 1,000 people)
 disorders of the lymph system due
to a viral infection (EBV-associated
lymphoproliferative disorder)
 coma
 seizures
 agitation
 blindness
 inflammation or damage of the nerve
of the eyes (optic neuritis; optic
neuropathy)
 heart failure
 irregular heart beat (arrhythmia)
 skin cancer
 skin and/or mucous coat reaction with
redness, inflammation, blistering and
tissue break down (Lyell‘s syndrome,
Stevens-Johnson syndrome)
Not known (frequency cannot be
estimated from available data)
 bleeding in the brain
 neurological disorders manifested
by headache, feeling sick (nausea)
and vomiting, seizures, visual
disturbances including vision loss,
changes in mental status (thinking
abnormal, confusion, altered
consciousness), and occasionally
neuromuscular disorders manifested
by muscle weakness in your limbs
(including irreversible partial or
complete paralysis) (symptoms of
leukoencephalopathy, acute toxic
leukoencephalopathy or posterior
reversible leukoencephalopathy
syndrome (RPLS)).
 bleeding in the lungs
 inflammation of the bladder, which
can cause pain when passing urine,
and can lead to blood in the urine
(haemorrhagic cystitis)
Reporting of side effects
If you get any side effects, talk to your
doctor, pharmacist or nurse. This includes
any possible side effects not listed in this
leaflet. You can also report side effects
directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard
By reporting side effects you can help
provide more information on the safety
of this medicine.

Marketing Authorisation Holder and
Manufacturer
Marketing Authorisation Holder
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
Manufacturer
Genzyme Ltd, 37 Hollands Road,
Haverhill, Suffolk, CB9 8PU, UK
This medicinal product is authorised
in the Member States of the EEA
under the following names:
Belgium Fludara
France Fludara
Germany Fludara
Greece Fludara
Ireland Fludara
Italy Fludara
The Netherlands
Fludara
Portugal Fludara
Spain Beneflur
UK Fludara
This leaflet was last revised in
November 2015
Local representative:
Sanofi
One Onslow Street, Guildford, Surrey,
GU1 4YS, UK
Tel: 0845 372 7101
email: uk-medicalinformation@sanofi.com

5. How to store Fludara
Keep this medicine out of the sight and
reach of children.
Do not use this medicine after the expiry
date which is stated on the carton and
vial label after “EXP”. The expiry date
refers to the last day of that month.
Unopened vials
This medicine does not require any
special storage conditions.
Reconstituted and diluted solutions
Reconstituted Fludara should be
used immediately or within 8 hours
of reconstitution if stored at room
temperature, or within 24 hours if stored
at 2 °C to 8 °C.

6. Contents of the pack and
other information
What Fludara contains
 The active substance is fludarabine
phosphate. Each vial contains 50 mg
fludarabine phosphate. 1 millilitre of
reconstituted solution contains 25 mg
fludarabine phosphate.
 The other ingredients are mannitol and
sodium hydroxide.
What Fludara looks like and contents
of the pack
Fludara is a sterile white powder for
solution for injection or infusion provided
in 10 ml glass vials. The powder is
reconstituted with water for injection and
further diluted. The reconstituted solution
is clear and colourless.
Fludara is available in packs containing
5 vials.

587538
Caution should be exercised in the
handling and preparation of the Fludara
solution. The use of latex gloves and
safety glasses is recommended to avoid
exposure in case of breakage of the
vial or other accidental spillage. If the
solution comes into contact with the skin
or mucous membranes, the area should
be washed thoroughly with soap and
water. In the event of contact with the
eyes, rinse them thoroughly with copious
amounts of water. Exposure by inhalation
should be avoided.

The medicinal product is for single use
only. Any unused medicinal product,
spillage or waste material should be
disposed of in accordance with local
requirements.

Measure bar should be 150mm at 100% scale

artwork.leicester@multipkg.com

Clearly mark any amendments on one proof and return to MPS

Warning! We cannot accept responsibility for any errors
in this proof after approval. Whilst we take extreme care
at all times to ensure accuracy to our clientʼs brief,
the final responsibility must be taken by our client.
IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING
FULL APPROVAL OF DESIGN AND TEXT.

Customer

Genzyme UK (Suffolk)

Description

FLUDARA IV 50MG Leaflet

Item Code

587538

Profile

GI200500

Size

200x500mm

Min. Point Size

9pt

Market

UK

Language

English

Proof By

louise.heel

Proof No.

2

Date

10/11/2015

Artwork No.

608991

Colours Used
50 gsm

Folded: 100x26mm

Pharma
Code

N/A

Process Black +25% + 15% tint
Keyline (does not print)

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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